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Genetic Interaction with Plasma Lipids on Alzheimer's Disease in the Framingham Heart Study.

TitleGenetic Interaction with Plasma Lipids on Alzheimer's Disease in the Framingham Heart Study.
Publication TypeJournal Article
Year of Publication2018
AuthorsPeloso GM, Beiser AS, DeStefano AL, Seshadri S
JournalJ Alzheimers Dis
Volume66
Issue3
Pagination1275-1282
Date Published2018
ISSN1875-8908
KeywordsAdult, Alleles, Alzheimer Disease, Cholesterol, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Incidence, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Triglycerides
Abstract

Epidemiological and genetic studies have pointed to the role of cholesterol in Alzheimer's disease (AD). We explored the interaction of a genetic risk score (GRS) of AD risk alleles with mid-life plasma lipid levels (LDL-C, HDL-C, and triglycerides) on risk for AD in the Framingham Heart Study (FHS). Mid-life (between the ages of 40-60 years old) lipid levels were obtained from individuals in the FHS Original and Offspring cohorts (157 cases and 2,882 controls) with genetic data and AD status available. Cox proportional hazards regression was performed to test the interaction between mid-life lipid levels and an AD GRS, as well as the individual contributing SNPs, on risk of incident AD adjusting for age, sex, and cohort. We found a significant interaction between a GRS of AD loci and log triglyceride levels on risk of clinical AD (p = 0.006), but no interaction of the GRS with HDL-C (p = 0.458) or LDL-C (p = 0.366). We then tested the interaction between the individual SNPs contributing to the GRS and log triglycerides. We found two SNPs that had interactions with triglycerides on AD risk that reached a p-value < 0.05 (rs11218343 and APOEɛ4). The association between some AD SNPs and risk of AD may be modified by triglyceride levels. Furthermore, sequential testing of a GRS with a set of traits on disease followed by testing individual SNPs for interaction provides a framework for narrowing the associations that need to be tested for interaction analyses. Replication is needed to confirm these findings.

DOI10.3233/JAD-180751
Pubmed Linkhttps://www.ncbi.nlm.nih.gov/pubmed/30412497?dopt=Abstract
page_expoExternal
Alternate JournalJ. Alzheimers Dis.
PubMed ID30412497
PubMed Central IDPMC6460910
Grant ListK01 HL125751 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
HHSN268201500001I / HL / NHLBI NIH HHS / United States
R01 AG054076 / AG / NIA NIH HHS / United States
R01 AG049607 / AG / NIA NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
U01 AG049505 / AG / NIA NIH HHS / United States
U01 AG052409 / AG / NIA NIH HHS / United States
RF1 AG059421 / AG / NIA NIH HHS / United States
R01 NS017950 / NS / NINDS NIH HHS / United States
UH2 NS100605 / NS / NINDS NIH HHS / United States
N02 HL64278 / HL / NHLBI NIH HHS / United States

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